Table 2

Multivariate Cox regression analyses with the adjustments of the covariates that we selected for the primary endpoint and each activity of daily living milestone using known predictive factors

	Primary endpoint		Loss of speech		Loss of swallowing function		Loss of upper limb function		Difficulty turning in bed		Loss of walking ability
	HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value
MRC score of neck flexors at registration	0.72 (0.62 to 0.83)	<0.001	0.78 (0.67 to 0.90)	0.001	0.80 (0.69 to 0.93)	0.003	0.76 (0.65 to 0.88)	<0.001	0.83 (0.70 to 0.98)	0.027	0.95 (0.79 to 1.15)	0.601
Age at registration (years)	1.03 (1.02 to 1.04)	<0.001	1.02 (1.01 to 1.03)	0.002	1.03 (1.01 to 1.04)	<0.001	1.01 (0.99 to 1.02)	0.264	1.01 (0.99 to 1.02)	0.265	1.00 (0.98 to 1.01)	0.890
Gender (male vs female)	1.14 (0.85 to 1.52)	0.381	0.85 (0.65 to 1.12)	0.247	1.13 (0.85 to 1.49)	0.398	1.27 (0.97 to 1.68)	0.088	1.01 (0.76 to 1.33)	0.947	0.85 (0.61 to 1.17)	0.309
Duration from onset to registration (years)	0.64 (0.57 to 0.72)	<0.001	0.72 (0.64 to 0.80)	<0.001	0.69 (0.62 to 0.77)	<0.001	0.82 (0.75 to 0.9)	<0.001	0.74 (0.65 to 0.85)	<0.001	0.75 (0.66 to 0.87)	<0.001
%VC at registration	0.98 (0.98 to 0.99)	<0.001	0.98 (0.97 to 0.99)	<0.001	0.98 (0.98 to 0.99)	<0.001	0.99 (0.98 to 1.00)	0.001	0.99 (0.99 to 1.00)	0.007	1.00 (0.99 to 1.00)	0.491
ALSFRS-R at registration	0.97 (0.94 to 0.99)	0.008	0.99 (0.97 to 1.02)	0.483	0.96 (0.93 to 0.98)	0.001	0.96 (0.94 to 0.98)	0.001	0.89 (0.86 to 0.92)	<0.001	0.91 (0.88 to 0.94)	<0.001
El Escorial criteria (probable or probable laboratory-supported)	0.72 (0.53 to 0.99)	0.043	0.61 (0.45 to 0.82)	0.001	0.76 (0.56 to 1.04)	0.087	0.67 (0.50 to 0.90)	0.007	0.71 (0.52 to 0.97)	0.031	0.63 (0.44 to 0.88)	0.008
Riluzole administration	1.02 (0.75 to 1.37)	0.916	1.09 (0.82 to 1.44)	0.551	0.97 (0.73 to 1.29)	0.843	0.95 (0.72 to 1.25)	0.694	0.84 (0.63 to 1.13)	0.258	0.94 (0.68 to 1.31)	0.721
Bulbar symptom at registration	0.91 (0.67 to 1.22)	0.524	2.04 (1.52 to 2.73)	<0.001	1.41 (1.06 to 1.86)	0.018	0.68 (0.50 to 0.93)	0.015	0.63 (0.47 to 0.84)	0.002	0.68 (0.49 to 0.96)	0.028

%VC, percent vital capacity: ALSFRS-R, revised amyotrophic lateral sclerosis functional rating scale.